Prader-Willi Syndrome

BOSTON, March 13, 2024 (GLOBE NEWSWIRE) -- Cerevance, a company focused on developing precision novel therapeutics for central nervous system (CNS) diseases, today announced plans to present a poster at the upcoming Alzheimer’s Research UK Conference, taking place in Liverpool, United Kingdom, March 20-21, 2024. Presentation details Title: The Two-Pore Potassium Channel KCNK13 (THIK1) as a Target to Modulate Neuroinflammation in Alzheimer’s Disease Overview: Cerevance’s NETSseq platform enables the identification of novel targets, such as KCNK13 (THIK1), from specific cell types in the human brain. Following the discovery of KCNK13, Cerevance has developed CVN293, a novel compound that selectively inhibits KCNK13 and reduces the release of IL-1β from microglia dependent on NLRP3. CVN293 shows promise in potentially addressing CNS conditions characterized by neuroinflammation, such as frontotemporal dementia (FTD), Amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease. Presenter: Heleen van ‘t Spijker, Jake Kinsella Poster Number: 10.10 About Cerevance Cerevance is focused on the development of precision treatments for central nervous system (CNS) disorders, prioritizing chronic neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis (ALS). Utilizing a large and growing collection of over 14,000 human brain tissue samples, Cerevance is generating an unprecedented level of expression and epigenetic data thereby enabling the company to identify the most promising targets for the next generation of treatments for CNS disorders. The company uses its proprietary NETSseq platform and advanced machine learning techniques to uncover the gene expression profiles of select cell types to identify novel targets that are uniquely expressed in relevant circuits affected by diseases or are altered in disease states. With the information obtained from its research, combined with the expertise of its team of scientists and drug developers, Cerevance is advancing multiple therapeutics that selectively modulate the discovered targets. These treatments are progressing through clinical development, with CVN424, CVN766, and CVN293 being the furthest along in the pipeline. CVN424 is a first-in-class non-dopamine therapy that shows promise in improving both motor and non-motor symptoms of Parkinson's disease and may also have disease-delaying effects. CVN766 is a potent antagonist of the orexin 1 receptor with high selectivity over the orexin 2 receptor which may benefit a variety of psychiatric conditions including schizophrenia, anxiety/panic, binge eating/obesity, substance use disorder, and Prader-Willi Syndrome. CVN293 is a novel blocker of potassium efflux in glia, regulating the inflammasome in individuals living with ALS and Alzheimer's disease. Cerevance’s robust pipeline aims to transform the lives of patients affected by CNS diseases. Contacts Cerevance: Johnna Simoes, ir@cerevance.com Media: Andrew Mielach, amielach@lifescicomms.com, +1-646-876-5868

An Acadia Pharmaceuticals drug that’s already approved for treating psychosis in Parkinson’s disease patients could not beat a placebo in a pivotal schizophrenia study, spelling the end of efforts to develop a medication the company once envisioned as having potential applications across a range of neurological disorders. The clinical trial failure announced Tuesday evaluated the drug, pimavanserin, as a treatment for negative symptoms of schizophrenia. The main goal was to show a change in score according to an assessment used to measure the disease’s symptoms. According to the preliminary results, the pimavanserin arm achieved a numerical change in score that was similar to the change reported in a prior Phase 2 study. But San Diego-based Acadia also said the placebo effect in Phase 3 was higher. Consequently, the score change in the Phase 3 trial was not enough to be statistically significant. Pimavanserin was initially approved in 2016, a regulatory decision that made the drug the first treatment for the hallucinations and delusions experienced by some Parkinson’s patients. In this indication, the once-daily capsule is marketed under the brand name Nuplazid. The Acadia drug is a small molecule designed to bind to 5-HT2A, a serotonin receptor that plays a role in psychosis. Parkinson’s psychosis was just the lead indication for the drug. The company conducted additional clinical trials to support potential label expansion. In 2021, the FDA rejected Acadia’s application for pimavanserin in dementia-related psychosis, pointing to a lack of statistical significance in some patient subgroups. The following year, FDA turned an application for the drug as a treatment for psychosis in Alzheimer’s patients, asking the company to conduct another clinical trial. Acadia instead discussed a resubmission based on additional analyses of existing clinical data. That resubmission was also rejected, leading the company to cease efforts to develop the drug for Alzheimer’s psychosis. The latest failure in schizophrenia marks the last time the company will try to expand pimavanserin’s label beyond Parkinson’s psychosis. “We are disappointed the trial did not meet its primary endpoint given the significant unmet need in patients with negative symptoms of schizophrenia,” Acadia CEO Steve Davis said in a prepared statement. “We will continue to analyze these data with our scientific advisors, but we do not intend to conduct any further clinical trials with pimavanserin.” Nuplazid accounted for $549.2 million in revenue in 2023, a 6.1% increase over sales of the product in 2022, according to Acadia’s financial reports. The company also has a new contributor to revenue, Daybue. A year ago, this drug became the first FDA-approved treatment for Rett syndrome, a rare genetic neurological disorder. In 2023, Daybue accounted for $177.2 million in sales. Acadia reported a cash position of $438.9 million at the end of 2023. In addition to supporting commercialization of Nuplazid and Daybue, the capital will also support development of a pipeline of drug candidates in various stages of development for central nervous system disorders and rare diseases. After the wind down of pimavanserin, Acadia’s next most advanced program is ACP-101, a drug in Phase 3 clinical trials for treating the insatiable appetite caused by the rare disease Prader-Willi syndrome. The pipeline also includes ACP-204, a novel molecule that has reached Phase 2 testing in Alzheimer’s disease psychosis.

- Study Did Not Meet Primary Endpoint SAN DIEGO--(BUSINESS WIRE)-- Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced top-line results from the Phase 3 ADVANCE-2 trial evaluating pimavanserin for the treatment of negative symptoms of schizophrenia. Pimavanserin did not demonstrate a statistically significant improvement over placebo on the study’s primary endpoint, the change from baseline to week 26 on the Negative Symptom Assessment-16 (NSA-16) total score (-11.8 vs. -11.1; p=0.4825; effect size=0.07). The safety and tolerability pro pimavanserin was consistent with previous clinical trials, showing a low rate of adverse events. “We are disappointed the trial did not meet its primary endpoint given the significant unmet need in patients with negative symptoms of schizophrenia,” said Steve Davis, Acadia’s Chief Executive Officer. “We will continue to analyze these data with our scientific advisors, but we do not intend to conduct any further clinical trials with pimavanserin. We want to thank the patients, their families, and the investigators for their contributions in this important study.” ADVANCE-2 was a 26-week double-blind, randomized, placebo-controlled study of 34 milligram pimavanserin in 454 adult patients with predominant negative symptoms of schizophrenia who had achieved control of positive symptoms with their ongoing antipsychotic treatment.​ ADVANCE-2 used the NSA-16 scale, designed to measure change on the wide range of predominant negative symptoms that patients experience, which looks at 16 different items in five subscales and covers symptoms such as blunted affect, poor socialization and lack of motivation.​ The change from baseline observed in the pimavanserin arm of ADVANCE-2 was similar to the change from baseline observed at the 34 milligram dose in ADVANCE-1 (-11.8 vs. -11.6); however, the placebo effect in ADVANCE-2 was higher than the placebo effect observed in ADVANCE-1 (-11.1 vs. -8.5). In ADVANCE-2, pimavanserin was well-tolerated with an adverse event rate of 30.4% compared with 40.3% for the placebo arm. About Acadia Pharmaceuticals Acadia is advancing breakthroughs in neuroscience to elevate life. For 30 years we have been working at the forefront of healthcare to bring vital solutions to people who need them most. We developed and commercialized the first and only FDA-approved drug to treat hallucinations and delusions associated with Parkinson’s disease psychosis and the first and only FDA-approved drug for the treatment of Rett syndrome. Our clinical-stage development efforts are focused on treating, Prader-Willi syndrome, Alzheimer’s disease psychosis and multiple other programs targeting neuropsychiatric symptoms in central nervous system disorders. For more information, visit us at Acadia.com and follow us on LinkedIn and Twitter. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements other than statements of historical fact and can be identified by terms such as “intends,” “may,” “will,” “should,” “could,” “would,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “projects,” “predicts,” “potential” and similar expressions (including the negative thereof) intended to identify forward-looking statements. Forward-looking statements contained in this press release, include, but are not limited to, statements about: (i) our clinical development plans related to pimavanserin and (ii) the safety pro pimavanserin. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors that may cause our actual results, performance or achievements to differ materially and adversely from those anticipated or implied by our forward-looking statements. Such risks, uncertainties, assumptions and other factors include, but are not limited to: our dependency on the continued successful commercialization of NUPLAZID and DAYBUE and our ability to maintain or increase sales of NUPLAZID or DAYBUE; our ability to generate or obtain the necessary capital to fund our clinical development plans; the timing and results of our clinical trials; our ability to maintain, protect and enhance our intellectual property; and our ability to continue to stay in compliance with applicable laws and regulations. Given the risks and uncertainties, you should not place undue reliance on these forward-looking statements. For a discussion of these and other risks, uncertainties, assumptions and other factors that may cause our actual results, performance or achievements to differ, please refer to our annual report on Form 10-K for the year ended December 31, 2023 filed with the Securities and Exchange Commission on February 28, 2024, as well as our subsequent filings with the Securities and Exchange Commission from time to time. The forward-looking statements contained herein are made as of the date hereof, and we undertake no obligation to update them after this date, except as required by law.